Low-dose Thoracic Radiotherapy Followed by Adebrelimab Plus Chemotherapy, and Then Sequential Maintenance Therapy With Adebrelimab for Extensive-stage Small Cell Lung Cancer

Официальное название

Efficacy and Safety of Low-dose Thoracic Radiotherapy Followed by Adebrelimab Plus Chemotherapy and Sequential Adebrelimab Maintenance Therapy for Extensive-stage Small Cell Lung Cancer: A Prospective, Multicenter Phase II Study

Обзор

This study is a multicenter, prospective investigation aiming to evaluate the efficacy and safety of low-dose radiotherapy (15Gy/1.5 Gy bid × 10 fractions) combined with 4-6 cycles of systemic chemotherapy concurrently with Adebrelimab, followed by Adebrelimab maintenance therapy for up to two years, in subjects with extensive-stage small cell lung cancer (ES-SCLC). Additionally, immunohistochemical detection of the expression levels of four key transcriptional proteins-YAP1, NEUROD1, ASCL1, and POU2F3-will be performed to guide the molecular subtyping of SCLC. Based on these findings, we will explore the differential therapeutic outcomes of this regimen across distinct molecular subtypes (A/N/P/Y/I/AN/QN), with the goal of identifying the subject population most likely to benefit from this treatment modality, thereby optimizing clinical decision-making.

Подробное описание

This study plans to prospectively enroll 43 subjects with extensive-stage small cell lung cancer (ES-SCLC) without malignant pleural effusion from multiple centers. All subjects will first receive low-dose radiotherapy (DT 15 Gy, 1.5 Gy/fraction × 10 fractions, BID). Within one week after radiotherapy completion, subjects will receive 4-6 cycles of systemic chemotherapy (EP or EC regimen) combined with adebrelimab (anti-PD-L1 antibody), followed by adebrelimab maintenance therapy for two years. Through this regimen, we aim to achieve survival outcomes comparable to or even superior to those of the MATCH study from West China Hospital (median PFS 6.9 months, median OS 16.9 months) and the NCT04562337 study from Shandong Cancer Hospital (median PFS 10.1 months, median OS 21.4 months), with manageable toxicity profiles.

Additionally, immunohistochemistry (IHC) will be performed to detect the expression levels of four key transcriptional proteins-YAP1, NEUROD1, ASCL1, and POU2F3-which are used to guide the molecular subtyping of small cell lung cancer. Based on these results, we will investigate the differential efficacy of this treatment regimen across distinct molecular subtypes (A/N/P/Y/I/AN/QN), with the goal of identifying the subject population most likely to benefit from this approach and ultimately better serving clinical practice.

Вмешательства

• Препарат Etoposide
  Etoposide 100 mg/m² on days 1-3 plus cisplatin 25 mg/m² on days 1-3, every 3 weeks (q3w), or etoposide 100 mg/m² on days 1-3 plus carboplatin AUC 5 on day 1, every 3 weeks (q3w).
• Препарат Cisplatin
  Etoposide (100 mg/m²) and cisplatin (25 mg/m²) were administered on days 1-3 of each 3-week cycle.
• Препарат Carboplatin
  Etoposide (100 mg/m²) was given on days 1-3 and carboplatin (AUC 5) on day 1 of each 3-week cycle.
• Препарат Adebrelimab
  20 mg/kg intravenously on day 1, repeated every 21 days (q3w). Administered concurrently with chemotherapy for 4-6 cycles, followed by maintenance monotherapy for up to 2 years.
• Лучевая терапия Thoracic Radiotherapy
  All subjects will first receive low-dose radiotherapy (DT 15 Gy, 1.5 Gy per fraction × 10 fractions, BID). Within one week after radiotherapy completion, they will receive 4-6 cycles of systemic chemotherapy (EP or EC regimen) combined concurrently with adebrelimab. Following the 4-6 cycles of chemo-immunotherapy, adebrelimab maintenance therapy will be continued for two years.

Первичные конечные точки

• Progression-Free Survival（PFS） [Срок оценки: From the date of first radiotherapy to the date of first documented disease progression, metastasis.]

Вторичные конечные точки (5)

• Overall Survival (OS) [Срок оценки: From date of first radiotherapy to date of death from any cause, assessed up to 36 months.]
• Overall Response Rate (ORR) [Срок оценки: Baseline (within 28 days prior to first dose), then every 8 weeks (±7 days) from radiotherapy initiation until 2 years post-treatment.]
• Disease Control Rate (DCR) [Срок оценки: Baseline (within 28 days prior to first dose), then every 8 weeks (±7 days) from radiotherapy initiation until 2 years post-treatment.]
• Incidence of Treatment-Emergent Adverse Events [Срок оценки: From date of first low-dose radiotherapy to 30 days after last dose.]
• To investigate the association between distinct molecular subtypes and clinical outcomes, including prognosis and treatment-related toxicity. [Срок оценки: Baseline: collect tumor tissue (archived FFPE or fresh biopsy) prior to treatment initiation; prognosis follow-up until progression or death (imaging q6w, survival q3m); toxicity monitoring until 30 days post-last dose (recorded at each visit).]

Критерии участия

Критерии включения

• Age ≥18 years and ≤75 years;
• Histologically or cytologically confirmed SCLC;
• No malignant pleural effusion or pericardial effusion;
• No prior history of thoracic radiotherapy or thoracic surgery;
• No prior systemic anti-tumor therapy;
• ECOG performance status 0-2, with a life expectancy of ≥12 weeks;
• At least one measurable lesion per RECIST 1.1 criteria;
• No history of interstitial pneumonia;
• No history of immune-related pneumonitis;
• No history of autoimmune diseases;
• No history of significant active pulmonary infection;
• No use of corticosteroid therapy within 14 days prior to enrollment;
• No Grade ≥3 hematologic toxicity or hepatic/renal impairment;
• No brainstem metastases and no significant neurological symptoms;
• For subjects with coexisting HBV/HCV infection, hepatic impairment ≤ Grade 1 after prior active antiviral therapy;
• All subjects have provided written informed consent;

Критерии исключения

• Presence of interstitial pneumonia or infectious fever prior to treatment;
• Comorbid autoimmune diseases or long-term oral corticosteroid use (including those who received oral corticosteroids within 14 days prior to treatment);
• Prior history of thoracic radiotherapy or thoracic surgery;
• Presence of Grade ≥3 hematologic toxicity or hepatic/renal impairment;
• Hypersensitivity to adebrelimab;
• Significant respiratory symptoms that preclude tolerance to radiotherapy;
• Active hepatitis B or C infection, currently on antiviral therapy, and with liver function impairment of Grade 2 or above;
• Presence of pleural effusion or pericardial effusion;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07583550 · 2026 049 A

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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